Protease inhibitor (Pi) phenotype, have been determined using isoelectric focusing on polyacrylamide gel in populations of normal subjects and patients with rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome and hepatocellular carcinoma. The incidence of aberrant (non-MM) phenotypes was not abnormal in any of the four diseases studied, suggesting that alpha-l-antitrypsin deficiency does not play a major role in the pathogenesis of any of these diseases. Using standard tracer methodology to study the turnover of a plasma protein,indices the metabolism of the M and Z alpha-1-antitrypsin molecules have been determined in normal subjects (Pi phenotype MM) and patients with alpha-1-antitrypsin deficiency (Pi phenotype ZZ).